White F J, Joshi A, Koeltzow T E, Hu X T
Department of Neuroscience, Finch University of Health Sciences, Chicago Medical School, Illinois 60064-3095, USA.
Neuropsychopharmacology. 1998 Jan;18(1):26-40. doi: 10.1016/S0893-133X(97)00093-6.
We investigated the ability of dopamine D1 and D2 class receptor antagonists to prevent the induction of behavioral sensitization to cocaine. The D2 receptor antagonist eticlopride failed to prevent the induction of cocaine sensitization. An intermediate dose of the D1 receptor antagonist SCH 23390 (0.1 mg/kg) appeared to prevent the induction of cocaine sensitization when tested after 3 days of withdrawal, but sensitization was clearly evident after 10 days of withdrawal. High doses of SCH 23390 alone produced supersensitivity to the behavioral effects of cocaine and to the inhibitory effects of D1 receptor agonists on nucleus accumbens neurons. Co-administration of eticlopride and SCH 23390 also failed to prevent the induction of cocaine sensitization. SCH 23390, but not eticlopride, prevented the expression of cocaine sensitization. We conclude that dopamine receptors are either not involved in the induction of cocaine sensitization or that redundant mechanisms exist to produce the same neuroadaptations.
我们研究了多巴胺D1和D2类受体拮抗剂预防对可卡因行为敏化诱导的能力。D2受体拮抗剂依托必利未能预防可卡因敏化的诱导。当在撤药3天后进行测试时，中等剂量的D1受体拮抗剂SCH 23390（0.1毫克/千克）似乎可预防可卡因敏化的诱导，但在撤药10天后敏化明显可见。单独使用高剂量的SCH 23390会对可卡因的行为效应以及D1受体激动剂对伏隔核神经元的抑制效应产生超敏反应。同时给予依托必利和SCH 23390也未能预防可卡因敏化的诱导。SCH 23390可预防可卡因敏化的表达，但依托必利不能。我们得出结论，多巴胺受体要么不参与可卡因敏化的诱导，要么存在冗余机制来产生相同的神经适应性变化。
